Gut adaptation and the insulin-like growth factor system: Regulation by glutamine and IGF-I administration

Intestinal adaptation after extensive small bowel resection in rats is augmented by the provision of diets supplemented with the amino acid glutamine (Gin) or by administration of insulinlike growth factor-I (IGF-I). The goal of this study was to investigate potential synergistic effects of Gin and IGF-I on postresection ileal hyperplasia. Rats underwent 80% small bowel resection (SBR) and then were fed low-Gin or L-Gln-enriched diets and subcutaneously given recombinant human IGF-I or vehicle for 7 days. Gin and IGF-I each significantly enhanced adaptive ileal hyperplasia (DNA content) compared with rats receiving vehicle and low-Gin diet. Ileal DNA content was highest when IGF-I was administered together with Gin supplementation. Combined IGF-I plus Gin synergistically increased ileal weight and protein content. This was associated with higher plasma concentrations of IGF-I and Gin than observed when IGF-I or Gin was given individually. Ileal IGF-I mRNA expression rose nearly twofold during gut adaptation after SBR; this response was augmented with IGF-I administration but was unaltered by Gin feeding. In contrast, dietary Gin, but not IGF-I therapy, prevented a decrease in hepatic IGF-I mRNA induced by SBR. We conclude that parenteral IGF-I and enteral Gin have both individual and synergistic effects on ileal adaptation after massive small intestinal resection. These findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance intestinal adaptation and possibly reduce the severity of short bowel syndrome after intestinal resection.